Organotypic cultures of central and peripheral neural tissues will be used in conjuction with muscle explants as model systems to supplement and analyze in situ studies in cellular neurophysiology, neuropathology, and related disciplines. The unique geometry of these relatively two-dimensional cellular arrays in vitro will be exploited to facilitate close correlation of the bioelectric and cytologic propertiesof cultured neurons and muscle cells under avariety of experimental conditions, including systematic application of patterned electric stimuli as well as pharmacologic, immunologic and other selective physico-chemical agents. Since neural tissues from embryonic, fetal or neonatal mammals (including human) can adapt well to culture conditions, emphasis will be placed on physiologic studies during the differentiation and development of these isolatedgroups of neural (and related) cells. Electron microscopy will be utilized, together with autoradiographic and cytochemical techniques, to analyze the ultrastructural basis of the functional synaptic networks which form at critical stages of maturation in vitro. These model systems will permit more direct analyses of inductive, trophic or other chemical factors which may underly synaptogenesis and formation of organized cell assemblies, with patterned neuronal circuit connections. Experiments leading to "plastic" alterations of CNS tissues associated with functional shaping of these behavioral network models will also be carried out under rigorous control. Electrophysiologic studied during critical stages of CNS development in vitro will be coordinated with parallel experiments in situ, where practicable.